The overall objective of this proposal is to understand the course of differentiation of erythriod cells in terms of membrane glycoproteins and evaluate cell membrane glycoproteins as onco-differentiation cell surface marker, shared by tumor cells and normal cells at an early stage of differentiation. Two major aspects will deal with: (1) Testing whether certain membrane glycoproteins can function as tumor-specific cell surface marker as well as specific marker for cells at an early stage of differentiation. We have analyzed cell surface glycoproteins of erythroblasts cultured in vitro and of human leukemic cell line K562 and found that some cell surface glycoproteins are expressed in both cells but not on mature erythrocytes. Further studies will be to isolate such glycoproteins, prepare antibodies specific to such glycoproteins and look at the distribution of such proteins in stem cell differentiation of normal individuals and patients. (2) Clarifying the structural change of lactosaminoglycan throughout the various ontogenic, differentiation and ongogenic stages. We have found that lactosaminoglycan displays a drastic structural change during ontogenesis. These structural changes can be analyzed distinctively by newly developed technique, cell surface labeling and endo-Beta-galactosidase digestion. This technique already played a key role in understanding the cell surface carbohydrate structure of erythroblasts and K562 cells. Further experiments will be structural studieson polylactosamine and its analogues of Band 3 and glycophorin to relate ontogenic change to the changes in differentiation and oncogenesis. In addition, the carbohydrate structure of a glycoprotein (Gp105), specifically present on K562 cells, will be characterized.